Rouzine I M, Sergeev R A, Glushtsov A I
Department of Molecular Biology and Microbiology, Tufts University, 136 Harrison Avenue, Boston, MA 02111, USA.
Proc Natl Acad Sci U S A. 2006 Jan 17;103(3):666-71. doi: 10.1073/pnas.0510016103. Epub 2006 Jan 5.
The organization of the cytotoxic T lymphocyte (CTL) response at organismal level is poorly understood. We propose a mathematical model describing the interaction between HIV and its host that explains 20 quantitative observations made in HIV-infected individuals and simian immunodeficiency virus-infected monkeys, including acute infection and response to various antiretroviral therapy regimens. The model is built on two modes of CTL activation: direct activation by infected cells and indirect activation by CD4 helper cells activated by small amounts of virus. Effective infection of helper cells by virus leads to a stable chronic infection at high virus load. We assume that CTLs control virus by killing infected cells. We explain the lack of correlation between the CTL number and the virus decay rate in therapy and predict that individuals with a high virus load can be switched to a low-viremia state that will maintain stability after therapy, but the switch requires fine adjustment of therapy regimen based on the model and individual parameters.
细胞毒性T淋巴细胞（CTL）反应在机体水平上的组织情况目前还知之甚少。我们提出了一个描述HIV与其宿主之间相互作用的数学模型，该模型解释了在HIV感染个体和猿猴免疫缺陷病毒感染猴子中所做的20项定量观察结果，包括急性感染以及对各种抗逆转录病毒治疗方案的反应。该模型基于CTL激活的两种模式构建：被感染细胞的直接激活和被少量病毒激活的CD4辅助细胞的间接激活。病毒对辅助细胞的有效感染会导致在高病毒载量下出现稳定的慢性感染。我们假设CTL通过杀死被感染细胞来控制病毒。我们解释了治疗中CTL数量与病毒衰减率之间缺乏相关性的原因，并预测高病毒载量的个体可以转换到低病毒血症状态，且该状态在治疗后将保持稳定，但这种转换需要根据模型和个体参数对治疗方案进行精细调整。
